TY - JOUR
T1 - A precision medicine approach to stress testing using metabolomics and microribonucleic acids
AU - Limkakeng, Alexander T.
AU - Rowlette, Laura Leigh
AU - Hatch, Ace
AU - Nixon, Andrew B.
AU - Ilkayeva, Olga
AU - Corcoran, David
AU - Modliszewski, Jennifer
AU - Griffin, Shannon Michelle
AU - Ginsburg, Geoffrey S.
AU - Voora, Deepak
N1 - Funding Information:
The current study was made possible by funding support via a Pilot Grant from the Emergency Medicine Foundation. Samples were collected in a prior study that was supported by an investigator-initiated grant from Abbott Laboratories. The authors retained possession of all data and decision on whether to publish at all times. GS Ginsburg reports having an unlicensed patent on a metabolomic finding. Ginsburg also serves on the Scientific Advisory Board for CardioDx. GS Ginsburg, AT Limkakeng and D Voora have received research funding from Abbott Laboratories. Limkakeng has also received prior research grants from Roche International, and Siemens Healthcare Diagnostics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Publisher Copyright:
© 2022 Future Medicine Ltd.
PY - 2022/7
Y1 - 2022/7
N2 - Both transcriptomics and metabolomics hold promise for identifying acute coronary syndrome (ACS) but they have not been used in combination, nor have dynamic changes in levels been assessed as a diagnostic tool. We assessed integrated analysis of peripheral blood miRNA and metabolite analytes to distinguish patients with myocardial ischemia on cardiac stress testing. We isolated and quantified miRNA and metabolites before and after stress testing from seven patients with myocardial ischemia and 1:1 matched controls. The combined miRNA and metabolomic data were analyzed jointly in a supervised, dimension-reducing discriminant analysis. We implemented a baseline model (T0) and a stress-delta model. This novel integrative analysis of the baseline levels of metabolites and miRNA expression showed modest performance for distinguishing cases from controls. The stress-delta model showed worse performance. This pilot study shows potential for an integrated precision medicine approach to cardiac stress testing. Plain language summary The study of small sequences of ribonucleic acids (miRNAs) and byproducts of cellular metabolism (metabolites) could help us to identify important cardiac conditions such as not enough blood and oxygen supply to the heart (acute coronary syndrome). We obtained blood samples from patients getting cardiac stress tests (a noninvasive test to see if the patient has enough blood flow to their heart) before and after their test, then compared the levels of miRNAs and metabolites in them. We compared the levels in patients who had abnormal stress tests with those that had normal tests. We believe this could be a model for a new type of cardiac stress test if validated in more patients. Tweetable abstract Can metabolomics + miRNAs augment imaging in cardiac stress tests? This study examines an integrative analysis of pre-A nd post-stress samples to determine if combining these data can help differentiate myocardial ischemia.
AB - Both transcriptomics and metabolomics hold promise for identifying acute coronary syndrome (ACS) but they have not been used in combination, nor have dynamic changes in levels been assessed as a diagnostic tool. We assessed integrated analysis of peripheral blood miRNA and metabolite analytes to distinguish patients with myocardial ischemia on cardiac stress testing. We isolated and quantified miRNA and metabolites before and after stress testing from seven patients with myocardial ischemia and 1:1 matched controls. The combined miRNA and metabolomic data were analyzed jointly in a supervised, dimension-reducing discriminant analysis. We implemented a baseline model (T0) and a stress-delta model. This novel integrative analysis of the baseline levels of metabolites and miRNA expression showed modest performance for distinguishing cases from controls. The stress-delta model showed worse performance. This pilot study shows potential for an integrated precision medicine approach to cardiac stress testing. Plain language summary The study of small sequences of ribonucleic acids (miRNAs) and byproducts of cellular metabolism (metabolites) could help us to identify important cardiac conditions such as not enough blood and oxygen supply to the heart (acute coronary syndrome). We obtained blood samples from patients getting cardiac stress tests (a noninvasive test to see if the patient has enough blood flow to their heart) before and after their test, then compared the levels of miRNAs and metabolites in them. We compared the levels in patients who had abnormal stress tests with those that had normal tests. We believe this could be a model for a new type of cardiac stress test if validated in more patients. Tweetable abstract Can metabolomics + miRNAs augment imaging in cardiac stress tests? This study examines an integrative analysis of pre-A nd post-stress samples to determine if combining these data can help differentiate myocardial ischemia.
KW - acute coronary syndrome
KW - biomarkers
KW - metabolomics
KW - miRNA
KW - precision medicine
KW - stress test
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85134854669&partnerID=8YFLogxK
U2 - 10.2217/pme-2021-0021
DO - 10.2217/pme-2021-0021
M3 - Article
C2 - 35466688
AN - SCOPUS:85134854669
SN - 1741-0541
VL - 19
SP - 287
EP - 297
JO - Personalized Medicine
JF - Personalized Medicine
IS - 4
ER -